rna-sequencing reveals unique transcriptional signatures of running and running-independent environmental enrichment in the adult mouse dentate gyrus

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ID: 195542
2018
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Abstract
Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running’s genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.
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grgoire2018frontiersrna-sequencing Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Catherine-Alexandra Grégoire;Catherine-Alexandra Grégoire;Catherine-Alexandra Grégoire;Stephanie Tobin;Stephanie Tobin;Brianna L. Goldenstein;Brianna L. Goldenstein;Brianna L. Goldenstein;Éric Samarut;Éric Samarut;Éric Samarut;Andréanne Leclerc;Anne Aumont;Pierre Drapeau;Pierre Drapeau;Pierre Drapeau;Stephanie Fulton;Stephanie Fulton;Karl J. L. Fernandes;Karl J. L. Fernandes;Karl J. L. Fernandes
Journal international journal of nanomedicine
Year 2018
DOI
10.3389/fnmol.2018.00126
URL
http://journal.frontiersin.org/article/10.3389/fnmol.2018.00126/full
Keywords
exercise social environment rna-sequencing dentate gyrus neuropsychiatry biological psychiatry

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